The use of balloon catheters to enlarge artherosclerotic blood vessels, as well as to counteract narrowing in ureters, urethras, bile ducts, fallopian tubes and the like, is well known in the art. In transluminal angioplasty, for example, a coronary artery that has become blocked with plaque (i.e., an artherosclerotic blood vessel) is enlarged through the use of a balloon catheter. This procedure has been found to be a therapeutic alternative to the surgical removal of the plaque and/or to bypass surgery.
More particularly, the balloon angioplasty procedure is generally carried out as follows. First, a balloon catheter is positioned within the restricted segment of the blood vessel. Then the catheter's balloon is inflated with a fluid (e.g. a gas or liquid) so as to compress the plaque and thereby enlarge the central lumen of the blood vessel. In this way blood flow through the vessel can be increased.
Unfortunately, such dilation of an artherosclerotic blood vessel can often cause serious damage to the blood vessel, due to the trauma associated with dilation. In particular, it has been found that the dilated blood vessel frequently has an excessive healing response, such that the blood vessel's central lumen subsequently renarrows. This frequently occurs within as little as six months after the dilation procedure is conducted.
Experimental studies have shown that administering anti-platelet, anti-coagulant, anti-proliferative and/or anti-inflammatory drugs to the site of the trauma can regulate the healing response of the tissue. Unfortunately, these drugs have traditionally been administered to the patient systemically. As a result, it has generally been necessary to administer relatively high dosages to the patient in order to achieve the desired concentrations of the drugs at the site of the trauma. These high dosage levels have sometimes caused serious side effects in the patient.
It has been recognized that the controlled delivery of these therapeutic agents directly to the trauma site would allow the desired dosages to be administered to the damaged tissue, without the occurrence of systemic toxicity. In fact, it has been found that the controlled delivery of appropriate medication directly to the trauma site is one of the most effective means of reducing the excessive healing response that causes restenosis in the dilated blood vessels.
Consequently, to avoid the dangers of systemic toxicity, various devices have been proposed to deliver medication directly to the side wall of a blood vessel.
For example, balloon catheters have been constructed where the body of the balloon is formed out of a permeable membrane. As a result, when these balloon catheters are positioned within a restricted segment of a blood vessel and their balloons subsequently inflated with an appropriate medication-containing fluid, the medication-containing fluid will pass through the wall of the balloon and into the adjacent wall of the blood vessel. In this way the desired medication can be delivered directly to the site of the angioplasty. Unfortunately, however, it has also been found that these fluid-permeable balloon catheters must generally use a relatively high fluid pressure in order to properly inflate their balloons and eject their medication-containing fluid. This pressure is at a magnitude such that it tends to cause additional damage to the wall of the blood vessel, which in turn leads to further excessive vascular healing response and hence to additional renarrowing of the blood vessel.
In another attempt to provide the local delivery of medication directly to the dilation site, encapsulated drugs have been deposited directly onto the inner wall of the blood vessel during the angioplasty procedure using a heated balloon catheter system. And in another technique, drugs have been impregnated into a hydrophilic coating which is placed on the catheter's balloon, so that the drugs are applied to the surrounding tissue during balloon inflation. Additionally, wire and/or biodegradable stents have been developed which can be impregnated with drugs so as to provide local drug delivery when those stents are deployed at the angioplasty site. Furthermore, it has also been shown that the controlled delivery of a drug to the exterior of the blood vessel by surgical techniques can help inhibit the renarrowing process (i.e., restenosis).
Unfortunately, all of the prior art devices and methods heretofore used to deliver therapeutic agents directly to the angioplasty site have suffered from one or more significant deficiencies. Until now, none have been completely effective in administering measured amounts of a therapeutic agent directly to the damaged tissue in a dilated blood vessel.